High doses of methylprednisolone are required for the treatment of collagenase-induced intracerebral hemorrhage in rats.

Methylprednisolone (MP) was evaluated for the treatment of intracerebral hemorrhage in a Sprague-Dawley rat model of cerebral hematoma induced by subcortical injection of collagenase. At 1 and 24 h after the injection, MP was administered intraperitoneally (IP) at a concentration of 10, 35, or 100 mg/kg. Control groups received saline IP at 1 and 24 h after the intracerebral injection of collagenase (positive controls) or saline (negative controls). Motor behaviour 24 h before and 24 h and 48 h after the intracerebral injection was evaluated by means of a neurologic exam and a rotarod treadmill test. The animals were euthanized at 48 h; brain water content was determined in half of the rats, and histopathological studies were done in the other half. Compared with the positive controls, the animals with collagenase-induced hematoma performed significantly better on the neurologic exam after treatment with 100 mg/kg of MP and on the rotarod test after treatment with 35 or 100 mg/kg of MP. The hematoma volume was significantly smaller (P < 0.002) after all doses of MP; however, the smallest volume was seen with 100 mg/kg. There were significantly fewer neutrophils (P < 0.01) within the hematoma in the MP-treated animals (maximum reduction with 100 mg/kg) than in the positive controls, but the numbers of reactive astrocytes did not differ significantly between the treatment groups. The number of necrotic neurons in the penumbra did not differ between the treatment groups; however, there were significantly fewer (P < 0.005) in the cerebral cortex in the group treated with 100 mg/kg of MP compared with the positive controls. These results suggest that high doses of MP administered shortly after occurrence of a cerebral hematoma are beneficial for the treatment of intracerebral hemorrhage.